This proposal is for purchase of a 500 MHz Fourier transform nuclear magnetic resonance (FT-NMR) spectrometer. The increased chemical shift dispersion, signal-to-noise ratio, and increased magnetic field strength of this instrument will make feasible the following projects. 5S RNA: First determination of secondary base-pair number, identify, and sequence for a ribosomal RNA--Marshall. Lactose Synthetase, Thrombin: Molecular mechanism of calcium binding (lactose synthetase) and elucidation of binding properties at catalytic center and fibrinogen recognition site (thrombin)--Berliner. Ergot Alkaloids, Antibiotics, Marine Toxins: Biosynthetic pathways, enzyme stereo-chemistry, and mechanisms of chemical carcinogenesis using 13C and 2H NMR of metabolites and synthetic homologs--Floss. Biologically Important Carbohydrates: semisynthetic antibiotics, cell-surface antigenic determinants, active components of heparin, dynamics of ring conformational equilibria in sugars, oligosaccharide antigenic determinants. Dodecahedrane (and other synthetic products): Rapid structural assignments based on 1H NMR to replace much slower (when available) x-ray structure analysis. As demonstrated by numerous comparisons of spectra of these systems at different magnetic field strengths, the above projects require NMR performance not possible even from the latest model 300 MHz instrument. Methods will include conventional 1H FT-NMR (all investigators), 13C NMR (Floss, Horton, Paquette), 31p NMR (Marshall), homonuclear 1H nuclear Overhauser experiments with water-suppressing excitation. (Berliner), laser CIDNP to characterize exposed residues on proteins and nuclei acids, variable-temperature NMR and two-dimensional proton and carbon NMR.